The research in this proposal to provide a fundamental understanding of the influence of route of reexposure on the total body burden and internal target tissue dosimetry of commonly encountered. Superfund contaminants, including trichloroethylene, perchloroethylene, 1,1- dichloroethylene, vinyl chloride, toluene, xylene, benzene, diethylbenzene isomers, and chloroform. Furthermore, since this research will involved extension of existing physiologically based pharmacokinetic models to describe the brain dosimetry following exposures, this effort will enhance the ability to accurately extrapolate animal studies to relevant human exposure scenarios and improve hazard and risk assessments. Exposure assessment studies will be conducted with human volunteers using a novel real-time breath analysis system to determine the uptake of any of the nine potential contaminants of study from tap water by each of three routes: inhalation, ingestion, and dermal contact. This data will be coupled with physiologically based pharmacokinetic (PBPK) modeling to determine the uptake kinetics and brain dosimetry. The resultant data from these comprehensive research projects within this Superfund program focused on development of biomarkers of susceptibility and response in potentially exposed populations. The specific research objectives are: 1. To generate physiologically based pharmacokinetic models to describe target organ dosimetry by route exposure. 2. To use the models to predict human dosimetry under environmentally relevant exposure conditions at characterized field study locations. 3. To conduct field studies to provide actual exposure assessments and target organ dose estimates by each route of exposure.